Radiation therapy is the most common modality of cancer treatment; across the world annually 50% of the cancer patients receive radiation administration. Generally beams of particles are used to treat malignant tissue, using photon (x-ray/γ-ray), or electron, which produce low linear-energy transfer to the tissue. These beams are generated usually by means of linear accelerators or radioactive sources. These types of radiotherapy or radiosurgery facilities are widely used in clinics and hospitals. However, the main problem is that, in conventional radiation therapy, it is difficult to eradicate the cancer cells successfully and tumour recurrence occur which causes therapeutic failure.
Generally beams of particles are used to treat malignant tissue in radiation therapy, most commonly photon (x-ray, γ-ray) or electron. These beams are generated using linear accelerators or radioactive elements. In conventional radiotherapy systems, each beamlet is steady from moment to moment and there is no arrangement of temporally perturbing or fluctuating the dose rate intensity of the beamlet momentarily with time (though intensity may differ among beams at different positions). In intensity-modulated radiotherapy, there may be inter-beamlet variation spatially (and not intra-beamlet variation temporally), and it is the latter intra-beamlet temporal fluctuation that is embodied in this invention. In existing accelerators, the beamlets from different angles are administered successively (unlike the simultaneous administration of all the beamlets together confocally on the tumour which is elucidated in this invention). In existing radioactive gamma-knife also, the intensity of the beamlets cannot the temporarily varied, however the proposed methodology incorporates their temporal fluctuation.
In existing radiotherapy protocols, the tumour cells are usually not eradicated and cancer recurrence generally ensues later. For instance, as mentioned earlier, an average 1 inch diameter tumour will still have, after the full standard conventional radiotherapy course, about 100 malignant cells (slow-growing tumours) or 10 malignant cells (fast-growing tumours), and it is these cells that multiply causing recurrence of the disease. Moreover, conventional dose schedule are arbitrary and not adapted to the radiobiological character of the tumour. Furthermore, normal tissue is also killed considerably, producing radiation toxicity, and in the brain there is toxic necrosis and gliosis, together with associated dementia and cognitive deterioration which is a serious side-effect of radiotherapy in neuro-oncology. Due to this reason one cannot use radiotherapy in brain tumours of very young children whose cognitive and mental development is ongoing.
Inventors develop three principles: fluctuative dosing, confocal beaming, and adapting to tumour tissue-specific radiobiological milieu. We synthesize the administration of these three approaches in an orchestrated symbiotic strategy. We tailor-make the treatment duration, the fluctuation level and the dose profiling, by adjusting the therapy to the tumour tissue itself. Thus the suggested technique ensures the selective killing of tumour cells and protecting the normal cells by using the following measures:                Confocal Beaming        Stochastic Perturbation that strikingly increases tumour cell kill but not appreciable normal cell kill        Reducing the radiotherapy treatment duration required to fully eliminate tumour cells        Diminishing the cumulative radiotherapy dose required for this elimination.        Decreasing total cumulative dose to decrease radiotoxicity and associated dementia.        Making radiotherapy a possible option in paediatric brain tumours, due to our reduceable cumulative dose.        
The above strategies do indeed maximize the therapeutic differential of radiotherapy.
The principle of adding optimal stochastic fluctuation (gaussian perturbation) to a therapeutic signal, has been studied by researchers for numerous clinical applications to increase efficiency of various therapeutic modalities, such as in pulmonary ventilation, stroke, muscular rehabilitation, deafness and hypertension. The said principle is referred to variously as stochastic resonance, noise-induced transition or stochastic activation. Furthermore, stochastic fluctuation of photon beam has also been used to alter efficiency of photochemical/photobiological effects where chemical/biochemical reactions are actuated by photons (light). However, there has been no record of therapeutic use of stochastic fluctuation of photobiological effects, such as in photon-tissue interaction in radiotherapy using x-ray or γ-ray.
Stochastically-modulated radiotherapy beaming as proposed in the present methodology, has not been used earlier, and there is no literature available regarding the use of stochastic dose-rate fluctuation of beam to maximize the therapeutic effect in radiotherapy. However, there have been earlier endeavours for upgrading the efficiency of radiotherapy using conventional optimization procedures on standard deterministic (non-stochastic) radiotherapy. Nevertheless there is only moderate improvement at most, the tumour cells are generally not eradicated and recurrence duly ensues. Under these conditions, the oncology and therapeutic radiology community, and more so the neuro-oncological community, do really appreciate the crucial need of novel radiotherapetic interventions which can radically eliminate tumour cells (which can be done by the proposed methodology).